Mineralocorticoids and Glucocorticoids Cooperatively Increase Salt Intake and Angiotensin II Receptor Binding in Rat Brain

Shelat, Suresh G.; King, Jennifer L.; Flanagan‐Cato, Loretta M.; Fluharty, Steven J.

doi:10.1159/000054436

Cited by 53 publications

(46 citation statements)

References 76 publications

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“…An important role for the MR is supported by recent data demonstrating that intracerebrovascular infusion of aldosterone reduced the gain of the baroreflex function in Dahl Salt-sensitive rats (4). Cooperative effects of simultaneous MR and GR occupation on angiotensin receptor expression and feedback inhibition of the hypothalamic pituitary adrenal axis have been described by others and could be important for glucocorticoid effects on central cardiovascular regulation (5,45). Furthermore, interactions between MRs and GRs on central cardiovascular regulation could explain some of the inconsistencies in the results of previous studies.…”

Section: Discussionmentioning

confidence: 87%

Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate

Bechtold¹,

Scheuer²

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Bechtold, Andrea G., and Deborah A. Scheuer. Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate. Am J Physiol Regul Integr Comp Physiol 290: R1003-R1011, 2006. First published November 3, 2005 doi:10.1152/ajpregu.00345.2005.-Systemic corticosterone (Cort) modulates arterial baroreflex control of both heart rate and renal sympathetic nerve activity. Because baroreceptor afferents terminate in the dorsal hindbrain (DHB), an area with dense corticosteroid receptor expression, we tested the hypothesis that prolonged activation of DHB Cort receptors increases the midpoint and reduces the gain of arterial baroreflex control of heart rate in conscious rats. Small (3-4 mg) pellets of Cort (DHB Cort) or Silastic (DHB Sham) were placed on the surface of the DHB, or Cort was administered systemically by placing a Cort pellet on the surface of the dura (Dura Cort). Baroreflex control of heart rate was determined in conscious male Sprague Dawley rats on each of 4 days after initiation of treatment. Plots of arterial pressure vs. heart rate were analyzed using a four-parameter logistic function. After 3 days of treatment, the arterial pressure midpoint for baroreflex control of heart rate was increased in DHB Cort rats (123 Ϯ 2 mmHg) relative to both DHB Sham (108 Ϯ 3 mmHg) and Dura Cort rats (109 Ϯ 2 mmHg, P Ͻ 0.05). On day 4, baseline arterial pressure was greater in DHB Cort (112 Ϯ 2 mmHg) compared with DHB Sham (105 Ϯ 2 mmHg) and Dura Cort animals (106 Ϯ 2 mmHg, P Ͻ 0.05), and the arterial pressure midpoint was significantly greater than mean arterial pressure in the DHB Cort group only. Also on day 4, maximum baroreflex gain was reduced in DHB Cort (2.72 Ϯ 0.12 beats ⅐ min Ϫ1 ⅐ mmHg Ϫ1 ) relative to DHB Sham and Dura Cort rats (3.51 Ϯ 0.28 and 3.37 Ϯ 0.27 beats ⅐ min Ϫ1 ⅐ mmHg Ϫ1 , P Ͻ 0.05). We conclude that Cort acts in the DHB to increase the midpoint and reduce the gain of the heart rate baroreflex function. corticosterone; nucleus of the solitary tract; glucocorticoid receptors; brain; stress ELEVATED GLUCOCORTICOIDS INCREASE the risk for cardiovascular disease (13,20,46,58,59). Accumulating evidence further indicates that altered glucocorticoid activity or sensitivity, even in the absence of elevated plasma glucocorticoid levels, may play a role in the etiology of human essential hypertension, a primary risk factor for cardiovascular disease (27,47,56,57). Altered glucocorticoid activity has also been implicated in the pathogenesis of metabolic syndrome, a condition whose symptoms include obesity, elevated blood pressure, and insulin resistance or diabetes (55). Genetic factors appear to increase sensitivity to the adverse cardiovascular effects of glucocorticoids, since several recently identified polymorphisms of the human glucocorticoid receptor (GR) gene have been linked to hypertension and cardiovascular disease (25,26,34,35). Complementing the data from humans, a glucocorticoid-dependent mechanism of hypertension has been demonstrated in several rat strains, including s...

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Section: Discussionmentioning

confidence: 87%

Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate

Bechtold¹,

Scheuer²

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The strongest evidence for glucocorticoid regulation of salt appetite came from studies examining NaCl intake and angiotensin II-receptor binding after administration of DOC and dexamethasone (Shelat et al, 1999b). Specifically, rats treated with DOC and dexamethasone consumed more NaCl than when given DOC alone.…”

Section: Central Interactions Of Aldosterone and Angiotensin IImentioning

confidence: 99%

Richter and sodium appetite: From adrenalectomy to molecular biology

Krause

Sakai

2007

Appetite

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Nearly three-quarters of a century ago, Curt Richter removed the adrenal glands from rats and noted that the animal's vitality was dependent on its increased consumption of sodium chloride. In doing so, Richter revealed an innate behavioral mechanism that serves to maintain the hydromineral balance of an animal faced with sodium deficit. This experiment and others like it, led to the development of a field of research devoted to the investigation of salt appetite. The following is a discussion of how Richter's initial observations gave birth to an evolving field that incorporates multiple approaches to examine the drive to consume sodium. KeywordsSalt appetite; Angiotensin; Aldosterone; Corticosterone; Richter The Discovery of Salt AppetiteAt the time that Richter began his career at Johns Hopkins University much of the research examining ingestive behavior focused on the responses of individual organs or closely coordinated systems. Richter's pioneering work initiated a fundamental paradigm shift that moved the focus to adaptations of the organism as a whole. Specifically, he was interested in changes in behavior that compensated for perturbations in the internal environment. His approach toward investigation of such behaviors was as thorough as it was fundamental. Richter manipulated diet, interfered with the nervous system, and removed or replaced glandular secretions in attempt to understand the nutritional, neural, and endocrine signals that contribute to behavior.Richter created disturbances in the nutritional or mineral content of the internal environment with dietary deficiency. Subsequently, "self selection" experiments were performed where choices of different minerals and nutrients were presented for consumption. More often than not, animals would consume minerals and nutrients in amounts that would alleviate their experimentally-induced deficiencies. One of the most striking behaviors that Richter observed was that of rats voluntarily ingesting salt when faced with sodium deficit. Sodium chloride was removed from the rats' food and they were given access to water and 3 % NaCl solution. The intake of the NaCl solution was approximately 1% of the total diet, which remarkably, is the

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“…The sites of action of ANG II that affect the sympathetic neural outflow could not be determined from the present study, but evidence from previous studies has suggested the involvement of the central nervous system (7,21,24,26,27,34,37) or sympathetic ganglia (3,10,11). The effect of circulating ANG II on the sympathetic nervous system has been postulated to be mediated via circumventricular organs, including the area postrema or the subfornical organs, which are regions that have no blood-brain barrier (7,21,24,26,27,34,37).…”

Section: Discussionmentioning

confidence: 56%

“…A possible explanation for the enhanced pressor response to ANG II observed in PA patients is an upregulation of ANG II receptors in the vasculature (31,32) and in the central and peripheral components of the sympa- (31,32) and in the brain (5,34,37), and then it induces an upregulation of ANG II receptors. Another possible explanation for the exaggerated pressor response to ANG II in PA patients is in part due to an elevation of serum sodium concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of circulating ANG II on the sympathetic nervous system has been postulated to be mediated via circumventricular organs, including the area postrema or the subfornical organs, which are regions that have no blood-brain barrier (7,21,24,26,27,34,37). In addition, ANG II has been shown to stimulate sympathetic ganglionic neurons (3,10,11).…”

Section: Discussionmentioning

confidence: 99%

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Does infusion of ANG II increase muscle sympathetic nerve activity in patients with primary aldosteronism?

Matsukawa¹,

Miyamoto²

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Patients with primary aldosteronism (PA) were shown to have suppressed muscle sympathetic nerve activity (MSNA) in our previous study. Although baroreflex inhibition probably accounts in part for this reduced MSNA in PA, we hypothesized that the lowered activity of the renin-angiotensin system in PA may also contribute to the suppressed SNA. We recorded MSNA in 9 PA and 16 age-matched normotensive controls (NC). In PA, the resting mean blood pressure (MBP) and serum sodium concentrations were increased, and MSNA was reduced. We examined the effects of infusion of a high physiological dose of ANG II (5.0 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ) on MSNA in 6 of 9 PA and 9 of 16 NC. Infusion of ANG II caused a greater pressor response in PA than NC, but, in spite of the greater increase in pressure, MSNA increased in PA, whereas it decreased in NC. Simultaneous infusion of nitroprusside and ANG II, to maintain central venous pressure at the baseline level and reduce the elevation in MBP induced by ANG II, caused significantly greater increases in MSNA in PA than in NC. Baroreflex sensitivity of heart rate, estimated during phenylephrine infusions, was reduced in PA, but baroreflex sensitivity of MSNA was unchanged in PA compared with NC. All the abnormalities in PA were eliminated following unilateral adrenalectomy. In conclusion, the suppressed SNA in PA depends in part on the low level of ANG II in these patients.angiotensin II IT IS UNCLEAR WHETHER OR NOT a neurogenic mechanism is involved in the development and maintenance of elevated blood pressure levels in cases of hypertension induced by mineralocorticoid (2,4,5,9,17,26,29,35). Previous studies in rats (2,4,5,29) demonstrated the importance of the sympathetic nervous system or the central nervous system in the pathogenesis of hypertension caused by an excess of mineralocoticoid; central administration of aldosterone caused hypertension in rats (4, 5). However, recent studies in sheep did not support a role of the brain or the sympathetic nervous system in blood pressure elevation induced by the administration of aldosterone (17,35). Some clinical studies have estimated sympathetic nerve activity during the administration of mineralocorticoid (9, 26) or the nerve activity in patients with primary aldosteronism (PA), a type of human mineralocoticoid hypertension (1,8,18,20). Previous clinical studies, including a direct recording of sympathetic nerve activity in our previous study (18) and power spectral analysis of blood pressure (20), suggested a decrease in sympathetic nerve activity in PA patients. However, no studies on directly recorded sympathetic nerve activity in PA patients exist, or the mechanisms of the abnormality of nerve activity in PA were not clarified.Circulating ANG II has been reported to increase sympathetic nerve activity in animals (24, 27) and humans (11,14). Previous animal studies suggest that ANG II stimulates sympathetic nerve activity via sympathetic ganglia (3, 10, 11) and the central nervous system (24, 27). In our previous human studies with norm...

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Mineralocorticoids and Glucocorticoids Cooperatively Increase Salt Intake and Angiotensin II Receptor Binding in Rat Brain

Cited by 53 publications

References 76 publications

Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate

Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate

Richter and sodium appetite: From adrenalectomy to molecular biology

Does infusion of ANG II increase muscle sympathetic nerve activity in patients with primary aldosteronism?

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